The present invention relates to the treatment of female sexual dysfunction, and more particularly to a novel prostaglandin based composition therefore and the use thereof for treating female sexual dysfunction.
Female sexual dysfunction is not a well defined clinical entity, but can be characterized as the equivalence of male erectile dysfunction i.e. the inability of the female to reach sexual satisfaction. In contrast to the mechanism and etiology of male erectile dysfunction which have been extensively studied, only little is known about female sexual dysfunction; however, a reasonable hypothesis is inadequate vasodilatory capacity of the external genitals. Thus local drugs that restore the vasodilatory capacity of the genitals to the appropriate stimuli can be anticipated to improve the female sexual function. The prevalence of female sexual dysfunction is largely unknown, and dependent on age, but generally it can be estimated that such dysfunction is common e.g. amongst post menopausal women. Currently there is no adequate treatment of female sexual dysfunction other than hormonal treatment in post menopausal women.
While it is understood that many drugs with vasodilatory capacity administered e.g. orally may have effect on the genitals, and that certain systemic drugs e.g. sildenafil used for male erectile dysfunction, may have beneficial effect also for the treatment of female sexual dysfunction, it is a clear advantage if the drugs can be administered locally in the genital tract to avoid systemic side-effects.
We have now unexpectedly found that certain prostaglandin analogues of the E-type, more specifically agonists of the EP2 prostanoid receptor, exert good relaxant effect in the penile cavernous tissue, and in blood vessels while exhibiting markedly reduced pain inducing effect typical for many prostaglandins. Since the female external genitals embryologically correspond to the male genitals such as the penis, and expansive cavernous tissue is present in the genitals of both sexes it is very likely that the effect of certain prostaglandin analogues is fundamentally similar in the male and female. Such drugs may therefore also be used to treat female sexual dysfunction.
In particular we have found that PGE2 analogues substituted in carbon 18, 19 or 20 with hydroxyl (OH) exert beneficial effect, and especially one analogue, namely 19R-OH-PGE2, exhibited a surprisingly advantageous effect with respect to relaxation of cavernous tissue and blood vessels without inducing pain as studied in an animal model.
Thus, in a first aspect, the present invention provides a composition for the treatment of female sexual dysfunction, comprising a prostaglandin which is a selective EP2 or EP4 receptor agonist, or an active derivative, including the free acid, or a salt or an ester thereof, optionally together with a physiologically acceptable carrier or vehicle.
In a second aspect, the invention provides a method of treating female sexual dysfunction, which method comprises administering a therapeutically active and physiologically acceptable amount of the composition to an individual in need thereof.
In a third aspect, the invention provides the use of a selective EP2 or EP4 receptor agonist, or an active derivative including the free acid, a salt or an ester thereof, for the preparation of a medicament for the treatment of female sexual dysfunction.